Increased Cathepsin S activity associated with decreased protease inhibitory capacity contributes to altered tear proteins in Sjögren's Syndrome patients.

Cathepsin S (CTSS) activity is elevated in Sjögren's Syndrome (SS) patient tears. Here we tested whether protease inhibition and cystatin C (Cys C) levels are reduced in SS tears, which could lead to enhanced CTSS-driven degradation of tear proteins. CTSS activity against Cys C, LF and sIgA was tested in SS or healthy control tears. Tears from 156 female subjects (33, SS; 33, rheumatoid arthritis; 31, other autoimmune diseases; 35, non-autoimmune dry eye (DE); 24, healthy controls) were analyzed for CTSS activity and Cys C, LF, and sIgA levels. Cys C and LF showed enhanced degradation in SS tears supplemented with recombinant CTSS, but not supplemented healthy control tears. CTSS activity was significantly increased, while Cys C, LF and sIgA levels were significantly decreased, in SS tears compared to other groups. While tear CTSS activity remained the strongest discriminator of SS in autoimmune populations, combining LF and CTSS improved discrimination of SS beyond CTSS in DE patients. Reductions in Cys C and other endogenous proteases may enhance CTSS activity in SS tears. Tear CTSS activity is reconfirmed as a putative biomarker of SS in an independent patient cohort while combined LF and CTSS measurements may distinguish SS from DE patients.

Diagnosis of latent tuberculosis infection with T-SPOT(®).TB in a predominantly immigrant population with rheumatologic disorders.

PURPOSE: The objective of this study is to compare how likely positive tuberculin skin test (TST) and T-SPOT(®).TB (TSPOT) results predict risk factors for tuberculosis in a predominantly immigrant patient population at risk of latent TB infection (LTBI) and with rheumatologic conditions requiring immunomodulatory therapy (IMT). METHODS: Prospective study conducted at a referral rheumatology clinic. Inclusion criteria included patients on various IMT, including immunosuppressive drugs that could predispose to TB progression. We studied risk factors associated with LTBI, test results, and tests' agreement. RESULTS: We studied 101 patients. Eighty (79.2 %) were from countries where TB is prevalent and Bacille Calmette-Guérin vaccination is placed routinely. Seventy-four (73.3 %) had rheumatoid arthritis and 92 (90.7 %) were on IMT. Among patients with both TST and TSPOT results, 25 (30.9 %) were TST(+) and 20 (24.7 %) had TSPOT(+) results. Fifteen patients (18.5 %) had TST(+)/TSPOT(+) results, and 51 (63.0 %) had TST(-)/TSPOT(-) results (agreement = 81.5 %; kappa = .54 [95 % CI, .34-.74; P < .001]). Each TSPOT(+) and TST(+) results were independently associated with immigrant status and prior residence in a TB prevalent country after adjustment for immunosuppressive therapy: Adjusted OR(TSPOT+)=6.6 (95 % CI, 1.2-123.3; P = .027); and adjusted OR(TST+)=11.2 (95 % CI, 2.0-209.5; P = .003). Seven out of 10 TST(+)/TSPOT(-) cases had a TST ≥15 mm induration, including three cases with history of TST conversion. CONCLUSIONS: TST(+) and TSPOT(+) results predict risk factors associated with LTBI independent of immunosuppressive IMT. Some TST(+)/TSPOT(-) results were unlikely to be false-negatives. The combined use of TST and TSPOT appears to be a reasonable diagnostic strategy to evaluate for LTBI in this population.

Tear cathepsin S as a candidate biomarker for Sjögren's syndrome.

OBJECTIVE: The diagnosis of Sjögren's syndrome (SS) in routine practice is largely a clinical one and requires a high index of suspicion by the treating physician. This great dependence on clinical judgment frequently leads to delayed diagnosis or misdiagnosis. Tear protein profiles have been proposed as simple and reliable biomarkers for the diagnosis of SS. Given that cathepsin S activity is increased in the lacrimal glands and tears of NOD mice (a murine model of SS), the aim of this study was to explore the clinical utility of using tear cathepsin S (CTSS) activity as a biomarker for SS. METHODS: A method to measure CTSS activity in tears eluted from Schirmer's test strips was developed and validated. Schirmer's tests were performed and CTSS activity measurements were obtained in 278 female subjects, including 73 with SS, 79 with rheumatoid arthritis, 40 with systemic lupus erythematosus, 10 with blepharitis, 31 with nonspecific dry eye disease, and 12 with other autoimmune diseases, as well as 33 healthy control subjects. RESULTS: The median tear CTSS activity in patients with SS was 4.1-fold higher than that in patients with other autoimmune diseases, 2.1-fold higher than that in patients with nonspecific dry eye disease, and 41.1-fold higher than that in healthy control subjects. Tear CTSS levels were equally elevated in patients with primary SS and those with secondary SS, independent of the Schirmer's test strip values or the levels of circulating anti-SSA or anti-SSB antibodies. CONCLUSION: Markedly high levels of tear CTSS activity are suggestive of SS. CTSS activity in tears can be measured in a simple, quick, economical, and noninvasive manner and may serve as a novel biomarker for autoimmune dacryoadenitis during the diagnostic evaluation for SS.

Testicular descent related to growth hormone treatment.

An 8.7 year-old boy with cryptorchidism and growth hormone (GH) deficiency due to septooptic dysplasia presented testicular descent related to the commencement of hGH treatment. This case suggests a role for GH in testicular descent.